Multiple interactions of the 'transducer' govern its function in calpain activation by Ca2+.

TitleMultiple interactions of the 'transducer' govern its function in calpain activation by Ca2+.
Publication TypeJournal Article
Year of Publication2005
AuthorsBozoky, Z., A. Alexa, P. Tompa, and P. Friedrich
JournalBiochem J
Volume388
IssuePt 3
Pagination741-4
Date Published2005 Jun 15
ISSN1470-8728
KeywordsAmino Acid Sequence, Amino Acid Substitution, Animals, Binding Sites, Calcium, Calcium Signaling, Calpain, Catalytic Domain, Enzyme Activation, Humans, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Structure, Tertiary, Rats
Abstract

Typical calpains in mammals become activated on binding of 8-12 Ca2+ ions per enzyme molecule, giving an example of integrated, manifold regulation by calcium. Besides two identified Ca2+ sites in catalytic domain II and several EF-hand motifs in domains IV and VI, an acidic loop in the centrally positioned domain III seems to harbour Ca2+. The mediator of distant Ca2+-induced structural transitions is an elongated structural element, the 'transducer'. By site-directed mutagenesis along the transducer, we have generated various forms of rat m-calpain in which critical intramolecular interactions, as judged from the X-ray structure, would be abolished or modified. The kinetic parameters of these mutant enzymes support a model featuring shrinkage of transducer as a contributor to structural changes involved in calpain activation.

DOI10.1042/BJ20041935
Alternate JournalBiochem. J.
PubMed ID15569003
PubMed Central IDPMC1183452